Redox interactions between catalase and alcohol dehydrogenase pathways of ethanol metabolism in the perfused rat liver.
Alcohol metabolism via alcohol dehydrogenase (ADH) and catalase was studied in perfused rat livers by measuring the oxidation of methanol and butanol, selective substrates for catalase and ADH, respectively. In livers from fasted rats, basal rates of methanol uptake of 15 +/- 1 mumol/g/h were decreased significantly to 8 +/- 2 mumol/g/h by addition of butanol. Concomitantly, pyridine nucleotide fluorescence detected from the liver surface was increased by butanol but not methanol. Both effects of butanol were blocked by an inhibitor of ADH, 4-methylpyrazole, consistent with the hypothesis that elevation of the NADH redox state by butanol inhibited H2O2 production via NAD+-requiring peroxisomal beta-oxidation, leading indirectly to diminished rates of catalase-dependent methanol uptake. In support of this idea, both butanol and butyraldehyde inhibited H2O2 generation. The NADH redox state was also elevated by xylitol, causing a 75% decrease in rates of methanol uptake by livers from fasted rats. This effect was not observed in livers from fed rats unless malate-aspartate shuttle activity was reduced by infusion of the transaminase inhibitor aminooxyacetate. Taken together, these data indicate that generation of reducing equivalents from ADH in the cytosol inhibits H2O2 generation leading to significantly diminished rates of peroxidation of alcohols via catalase. This phenomenon may represent an important physiological mechanism of regulation of ethanol oxidation in intact cells.
Handler
J A
JA
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365.
Thurman
R G
RG
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000625:Aminooxyacetic Acid / Q000378:metabolism; D000818:Animals; D000440:Butanols / Q000378:metabolism; D002374:Catalase / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D000432:Methanol / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D013050:Spectrometry, Fluorescence; D013347:Subcellular Fractions / Q000378:metabolism; D014993:Xylitol / Q000378:metabolism
D000440:Butanols; D009829:Oleic Acids; D009243:NAD; D000625:Aminooxyacetic Acid; D019301:Oleic Acid; D000431:Ethanol; D006861:Hydrogen Peroxide; D000426:Alcohol Dehydrogenase; D002374:Catalase; D014993:Xylitol; D000432:Methanol